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Increased free intrasynaptosomal Ca2+by neurotoxic organometals: Distinctive mechanisms

  • Author(s): Komulainen, H
  • Bondy, SC
  • et al.
Abstract

Effects of several alkylmetals on free intrasynaptosomal Ca2+concentration, [Ca2+]i, were studied in vitro using the fluorescent Ca2+indicator fura-2. Neurotoxic alkylmetals methylmercury (Met-Hg), triethyllead (TEL), triethyltin (TET), and trimethyltin (TMT) (at 2.5-30 μm) increased [Ca2+]ito different degrees. Met-Hg was the most potent, elevating [Ca2+]i100-800 nm, dose dependently and significantly more than high K+(150 nm) or veratridine (350 nm). The effect of Met-Hg could not be inhibited with a Ca2+channel blocker, verapamil, nor with a Na+channel blocker, tetrodotoxin. Inhibition of the mitochondrial Ca2+uptake in situ with rotenone + oligomycin decreased the potency of Met-Hg to elevate [Ca2+]ibut did not change the resting [Ca2+]i. Met-Hg also slightly decreased synaptosomal ATP. TEL and TET elevated [Ca2+]iby 100-200 nm. The effect of TEL, but not that of TET, could be blocked with verapamil (36%) and veratridine (67%). TEL was less efficient in the presence of ouabain. Neither TEL nor TET had significant mitochondrial effects in situ contributing to [Ca2+]i. TMT increased [Ca2+]iless than TET while dimethyltin and methyltin were inactive. These results indicate that neurotoxic derivatives of alkylmetals studied increase [Ca2+]i. This occurs mainly either by nonspecific increase (Met-Hg, TET) of Ca2+leakage through the plasma membrane and/or specific interference with the mechanisms regulating Ca2+fluxes through the plasma membrane (TEL). © 1987.

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